1. Technical Field
This invention relates a process of making compounds useful as anti-inflammatory agents and intermediates thereof.
2. Background Information
WO 05/090333 discloses compounds of formula (I) and processes for preparing these compounds:

These compounds are useful for inhibition of the production of cytokines involved in inflammatory processes and for treating diseases and pathological conditions involving inflammation.
Particular product compounds containing imidazolyl rings were synthesized previously by a synthetic route shown below.

The amide coupling step is carried out with azide intermediate II to provide intermediate VIII. This is followed by reaction with the heteroaryl acetylene intermediate III in a suitable solvent such as EtOH, optionally in the presence of a copper salt such as CuSO4 with an appropriate reductant such as sodium ascorbate, and optionally while heating to provide the desired compound of formula (I).

The heteroaryl acetylene intermediate III may be prepared by reaction of intermediate V, where X is I, Br, Cl or −OSO2CF3, with trimethylsilylacetylene VI, in the presence of a suitable catalyst such as (PPh3)PdCl2, a copper salt such as CuI and a suitable base such as Et3N, followed by reaction with tetrabutylammonium bromide to remove the trimethylsilyl group. Alternatively, one may react a heteroaryl aldehyde VII with dimethyl 2-oxo-1-diazopropylphosphinate in the presence of a suitable base such as K2CO3 to provide intermediate III.